psychiatry as a neuroscience - mario maj

Psychiatry as a Neuroscience Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, Norman Sartorius Copyright # 2002 John Wiley & Sons Ltd. ISBNs: 0±471±49656±1 (Hardback); 0±470±84646±1 (Electronic) Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor Complutense University of Madrid, Spain Wolfgang Gaebel University of Du È sseldorf, Germany Mario Maj University of Naples, Italy Norman Sartorius University of Geneva, Switzerland Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, Norman Sartorius Copyright # 2002 John Wiley & Sons Ltd. ISBNs: 0±471±49656±1 (Hardback); 0±470±84646±1 (Electronic) Copyright # 2002 by John Wiley & Sons, Ltd., Baffins Lane, Chichester, West Sussex PO19 IUD, UK National 01243 779777 International (+44) 1243 779777 e-mail (for orders and customer service enquiries): cs-books@wiley.co.uk Visit our Home Page on: http://www.wiley.co.uk All Rights Reserved. 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Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, Norman Sartorius Copyright # 2002 John Wiley & Sons Ltd. ISBNs: 0±471±49656±1 (Hardback); 0±470±84646±1 (Electronic) Contents List of Contributors v Preface ix 1. Genetic Research in Psychiatry 1 Peter McGuffin 2. Molecular and Cellular Biology Research in Psychiatry 29 Stephen M. Stahl and Alexander B. Niculescu III 3. Brain Imaging Research in Psychiatry 59 Go È ran Sedvall and Stefan Pauli 4. Neuroendocrinological Research in Psychiatry 91 Charles B. Nemeroff and David A. Gutman 5. Neurophysiological Research in Psychiatry 125 John H. Gruzelier, Silvana Galderisi and Werner Strik 6. Neuropsychological Research in Psychiatry 181 Karen Ritchie and Marcus Richards 7. Neurobiology of Schizophrenia 197 Francine M. Benes and Carol A. Tamminga 8. Biological Research in Anxiety Disorders 237 Thomas W. Uhde and Ravi Singareddy 9. Biological Research on Dementias 287 Simon Lovestone Index 323 Acknowledgements 331 Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, Norman Sartorius Copyright # 2002 John Wiley & Sons Ltd. ISBNs: 0±471±49656±1 (Hardback); 0±470±84646±1 (Electronic) Contributors Francine M. Benes Laboratories for Structural Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA Silvana Galderisi Department of Psychiatry, University of Naples SUN, Largo Madonna delle Grazie, 80138 Naples, Italy John H. Gruzelier Department of Cognitive Neuroscience and Behaviour, Imperial College of Science, Technology and Medicine, St. Dunstan's Road, London W6 8RF, United Kingdom David A. Gutman Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322-4990, USA Simon Lovestone Departments of Old Age Psychiatry and Neuroscience, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, United Kingdom Peter McGuffin SGDP Research Centre, Institute of Psychiatry, De Cre- spigny Park, Denmark Hill, London, SE5 8AF, United Kingdom Charles B. Nemeroff Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322-4990, USA Alexander B. Niculescu III Neuroscience Education Institute and Depart- ment of Psychiatry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA Stefan Pauli Department of Clinical Neuroscience, Karolinska Institute and Hospital, 171 76 Stockholm, Sweden Marcus Richards MRC National Survey of Health and Development, University College Medical School, 1±19 Torrington Place, London WC1E 6BT, United Kingdom Karen Ritchie EPI 9930 INSERM, Ba à timent Recherche, CRLC Val d'Aur- elle, Parc Euromedecine, 326 rue des Apothicaires, 34298 Montpellier Cedex 5, France Go È ran Sedvall Department of Clinical Neuroscience, Karolinska Institute and Hospital, 171 76 Stockholm, Sweden Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, Norman Sartorius Copyright # 2002 John Wiley & Sons Ltd. ISBNs: 0±471±49656±1 (Hardback); 0±470±84646±1 (Electronic) Ravi Singareddy Department of Psychiatry and Behavioral Neurosci- ences, School of Medicine, Wayne State University, Detroit, MI 48231, USA Stephen M. Stahl Neuroscience Education Institute and Department of Psychiatry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA Werner Strik University Hospital of Clinical Psychiatry, Bollingenstrasse 111, Berne 60, 3000 Switzerland Carol A. Tamminga Department of Psychiatry, University of Maryland, Maryland Psychiatric Research Center, Box 21247, Baltimore, MD 21228, USA Thomas W. Uhde Department of Psychiatry and Behavioral Neurosci- ences, School of Medicine, Wayne State University, Detroit, MI 48231, USA vi CONTRIBUTORS Preface Psychiatry has come on to good terms with the rest of neurosciences only very recently. Since then the achievements have been impressive and the oppor- tunities unbelievable. Modern psychiatry was born at the end of the eighteenth century, to- gether with the rest of medical disciplines. This was when physicians abandoned old theories about diseases, many of them Galenic, and decided to describe what they saw, in accordance with the principles of modern science. Physicians learnt to see [1], and the site and causes of diseases were ascribed to organs. The title of Morgagni's seminal book, On the site and causes of diseases, investigated by anatomical methods, published in 1771, re- ferred precisely to this. The birth of psychiatry was more complex than that of the rest of medi- cine. It required three basic steps. The first was the delimitation of mental disorders from abnormal behaviours not accepted by society. It must be pointed out that the inmates in institutions such as the Ho à pitaux Generaux in France or asylums in Great Britain or Germany included not only men- tally ill individuals, but also others who were a nuisance to society. The clear-cut separation of these two populations is exemplified by the decision of the director of the Ho à pital Charenton in Paris, in the first years of the French Revolution, to discharge the famous Marquis de Sade. The author of Justine had spent many years as an inmate as a consequence of an order of King Louis XVI. The director's reason for discharging him was literally: ``He is not mad, his only madness is vice'' [2]. The second step was quite straightforward: to ascribe what was leftÐthat is, mental diseaseÐto an organ, quite naturally the brain. Although it seems that Voltaire coined the expression ``mental diseases are brain diseases'', it was the French alienist Esquirol [3] who introduced this concept in medi- cine. Immediately a third step was necessary, as psychiatry never fitted into a reductionistic medical model, and psychiatrists recognized among their patients some who seemed not to be suffering the consequences of brain disorders (on the contrary, their clinical manifestations seemed exagger- ations of everyday behaviour). In 1777 Cullen defined neuroses as preter- natural reactions [4], which could be translated as ``statistically abnormal reactions''. This introduced a dichotomy of mental disorders which has dominated up to very recent times, and is even present today. Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, Norman Sartorius Copyright # 2002 John Wiley & Sons Ltd. ISBNs: 0±471±49656±1 (Hardback); 0±470±84646±1 (Electronic) From then on psychiatry developed in a dualistic way. Dualism is attrib- uted to the French philosopher Descartes [5], who described two substances in human beings: one physical, which could be measured (res extensa), i.e. the body, and one characterized by thinking (res cogitans), i.e. the mind. It must be said that the trend to subdivide human nature is very ancient, and it is a powerful tool to explain the existence of evil, which according to Becker [6] is the main problem of the social sciences. This trend is present in gnostic philosophy and theology and in modern science. The German philosopher Dilthey [7] saw on the one side the sciences of nature (Naturwissenschaften), or natural sciences, ruled by the presence of causality, as in Newtonian physics. On the other side, however, he gave the status of sciences to other activities which today would be called ``soft science'', because they are unable to put forward causes and effects and experimental methods. His- tory is the best example. Here research delves into motives which lead to consequences, and between the motives and the consequences there is a space of uncertainty, which is in contrast to the immediate relation between cause and effect. These sciences were called by Dilthey ``sciences of the spirit'' (Geisteswissenschaften); other names applied to them are cultural or humanistic sciences. Following this line, Jaspers [8] distinguished two methods of psychopathological research: explanation, which is the search for causes, and understanding, which is the search for motives. This perspective shapes Kurt Schneider's [9] approach, which is at the core of current nosology, from DSM-III onwards. Schneider distinguished two kinds of mental disorders: the psychoses, which can be attributed to brain disorders, and the variations of the psychological way of being, essentially the neuroses and the psychopathic personalities. Looking closer and from the perspective of neuroscience, one of the branches of sciences of nature devoted to the nervous system, a series of problems appear. The organic and symptomatic psychoses are straightforward. The med- ical scientific model rules with no difficulties. Brain malfunctions and clin- ical manifestations correlate smoothly. Endogenous psychoses are different. They are characterized by manifest- ations that do not correspond to normal psychological phenomena, nor do they derive from them. They are, in the word of Jaspers, ``incomprehen- sible'', which means that there are no motives in them, and therefore they are not to be understood with the methods of humanistic sciences. Thus, they should have an explanation leading to the discovery of a cause following the principles of the sciences of nature. Well, yes and no. Endogenous psychoses, schizophrenia and mood disorders, are the most characteristic of psychiatric disorders, and also the most enigmatic. For many clinicians they are the Delphic oracle of psychiatry [10]; for neuropathologists they were their graveyard. Schneider again clarifies the difficulties when x PREFACE [AQ1] he says that endogenous psychoses are only sets of manifestations accepted by convention (he says that when first-rank symptoms are present the diag- nosis is what I call schizophrenia). Furthermore, the concept of ``symptoms'' does not apply properly to the clinical manifestations of endogenous psych- oses. Tellenbach [11], for instance, refers to them as ``phenomena''. To sum- marize, according to Schneider, the realm of schizophrenia and mood disorders can never be fully explained from the perspective of natural neuro- science. What about neurotic and personality disorders? Here Schneider lays stress on Griesinger's notion [12] that they are not brain diseases but vari- ations of the mode of being. This has often been misunderstood as meaning that there is no biological basis for them. The point is that there is a biological background, as there is in every psychological manifestation of our life, but it is not different from the one lying under normal psychological phenomena. Looking at the relationship between neuroscience and psychiatry from the other side, the problems have been also huge. First, there have been a series of paradigms, most of them too reductionist. Second, some methodo- logical problems may never be solved. The fight between localizationists and their opponents still goes on today in the discussion as to whether modules or circuits are the basic structures to investigate and correlate with psychological activity. As to the methods, the lack of sufficient animal models leads to the search for new ways of research. The different disciplines involved in the study of the nervous system have often developed in ignorance of the achievement of other disciplines. The concept of neuroscience as an integrated field of research is very young. Actually, it was born in 1969, when the Society for Neurosciences was created. Science is better at explaining abnormal phenomena than normal ones. Physiology was born out of physiopathology and psychology out of psy- chopathology. The first neuroscientific disciplines delved into diseases, led by neuropathology. Normality is considered at a later stage. However, this is not enough as other aspects come into consideration, development being the first. Part of the success of Ramo  n y Cajal was to study how the nervous system grew in order to understand the role of its structure in adulthood. During the last few decades the development of psychosocial sciences has reached a point where confluence with physiological and morphological sciences is a reachable target. Even Freud dared to write a highly speculative book on physiology for psychologists [13]. The founder of psychoanalysis was interested in developing an everyday scientific psychology and he did it from a physiological perspective. He was a physician, a pupil of Bru È cke, who was one of the four main disciples of Johannes Mu È ller, the introducer PREFACE xi [AQ2] [AQ3] [AQ4] of physiopathology in Germany. It is highly significant that Freud's transla- tors lost the everyday language which he used. For instance, where Freud wrote Seele (``soul''), the French translators wrote appareil psychique, leading to the notion that we have a ``psychological organ'' or ``system'', just as we have a digestive or sexual one. Today the situation is different from the one faced by Freud. There is much to be done, if only to drop the plural ``neurosciences'' in favour of the singular, a science integrating many different disciplines. This is the real challenge. One of the important recent changes lies in the fact that neurosci- entists are interested in how the brain functions while performing everyday tasks such as recognizing faces or familiar environments. To investigate this, it is necessary to analyse psychological and cognitive functions and to identify their basic elements. For instance, seeing is split down into the perceptions of lines, colour, inclination and so onÐelements that have different receptors at the retina, different pathways and cortical areas. Further cortical areas are able to recompose the different kinds of stimuli, and others, the secondary visual areas, to link them to other perceptions and memories. In this context, the question is not what can neuroscience do for psych- iatry, the answer to which is obvious, but the opposite: what can psychiatry do for neuroscience? In my opinion, psychiatry can help to overcome the limitations of dual- ism. To do this, two approaches seem particularly important. The first is to adopt a perspective beyond dualism. Following Lo  pez-Ibor Sr. [14] and others, we have tried to delve into the body experience, which is not the experience of a body separated from a soul, but the unitary experience of a corporality. Corporality is an incarnated mind, an animated body (using the Latin meaning of anima, ``soul''). The second approach is to define basic psychopathological disturbances which relate to basic psychological functions that could be linked to basic neurobiological activities. Here it is irrelevant whether these are cortical modules or cortico-subcortical pathways. Zutt [15], a great German repre- sentative of the anthropological trends in psychiatry, gives us two good examples of this perspective. The first is the Gerstmann syndrome, a well- known neurological syndrome appearing with lesions of left parietal cortex. The syndrome is characterized by finger agnosia, left-right agnosia and acalculia. A strange combination indeed. No so much, Zutt points out, if we take into account that the hands have an asymmetry which is the reflection of the asymmetry of nature, for instance of the spins of electrons. This is called ``cheirality'' (from the Greek word cheiros, ``hand''). Therefore there is a region of the brain which is able to recognize the hand and the fingers. Damage at this level interferes with the recognition of hand and fingers, and, simultaneously, with the other things we do with the internal- xii PREFACE [AQ5] [...]... this stage was an ideological battleground in psychiatry, with ``anti-psychiatrists'' such as R.D Laing arguing that schizophrenia was an understandable reaction to pathological family dynamics, and others, such as Thomas Szasz, arguing that schizophrenia was not an illness at all, but a ``myth'' created by doctors For many mainstream psychiatrists, the vital pieces of evidence that clinched the argument... century As far back as the 1820s, there was evidence that systematic attempts were being made to record the family histories of psychiatric patients For example, patients' case records at the Bethlem Royal Hospital in London, England, showed that one of the routine questions that the admitting doctor was   Psychiatry as a Neuroscience Edited by Juan Jose Lopez-Ibor, Wolfgang Gaebel, Mario Maj and Norman... hypercortisolism 105±6 hyperprolactinaemia 111 hyperthyroid states 101±2 hyperventilation, in panic disorder 241 hypothalamic-pituitary gonad axis see HPG axis hypothalamic-pituitary-adrenal axis see HPA axis hypothalamic-pituitary-end-organ axes 93±6 hypothalamic-pituitary-thyroid axis see HPT axis 327 hypothalamic-prolactin axis 111±12 hypothyroidism 42, 98±101 identical twins see twin studies immunology... facts'' in healthy psychological functioning and in disease The role of psychiatry as a neuroscience is to delve into the basic mechanisms underlying both normal and abnormal phenomena and, at the same time, to xiv PREFACE contribute to destigmatizing mental disorders so that they are not seen as something radically apart from the mental activity of everyday life, by understanding the adaptive mechanisms... it is generally valid [1] Twin studies have been important in demonstrating a genetic contribution to disorders such as schizophrenia [13], depression [14, 15] and manic-depressive disorder [16], as well as measures of normal behaviour such as cognitive ability as measured by IQ tests [17], and personality as measured by questionnaires [1] Twin studies have also been important in locating a strong genetic... 1.1 The first draft sequence of the entire human genome was published in 2000, and a more detailed initial sequencing and analysis of the human genome [49] shows that there are about 32 000±40 000 protein-coding genes in the human genome Although this is half as many as was once thought and only about twice as many as in worms or flies, it remains an enormous task to search through them and find the genes... penetrance Penetrance can be defined as the probability of manifesting a phenotype given a particular genotype Under Mendelian inheritance, penetrance is always either 0 or 1 Thus, in Table 1.2 we consider a disease (or more generally, a present/absent trait) where there is autosomal inheritance at a single locus with two alleles A1 and A2 There are therefore three genotypes, as shown in the table, and... very clear evidence of the extent to which a trait is influenced by genes In practice, the study of reared-apart identical (MZA) twins presents a number of problems The most important is that MZA twins are rare, and it is not usually possible to ascertain a series of such twins in a systematic fashion Thus, whereas twins reared together can be collected using hospital-based or population-based registers,... (1992) Caudate glucose metabolic rate changes with both drug and behaviour therapy for obsessive-compulsive disorder Arch Gen Psychiatry, 49: 681±689     Lopez-Ibor A. , Ortiz Alonso T., Encinas Mej as M., Fernandez A. , Maestu F., Â Ä Lopez-Ibor Alino J.J (2000) Avances en neuroimagen en el trastorno obsesivoÂ Ä compulsivo Actas Espanol Psiquiatr a, 28: 304±310  Janet P (1903) Les Obsessions et la Psychasthenie,... and again share a common environment Assuming that common environmental effects are as influential in DZ as in MZ pairs, any greater similarity regarding a given trait in MZ pairs should reflect the influence of genes Although this ``equal environments'' assumption has been criticizedÐbecause MZ twins may, for example, more often dress alike and share friends than DZ twinsÐvarious checks suggest that . 105±6 hyperprolactinaemia 111 hyperthyroid states 101±2 hyperventilation, in panic disorder 241 hypothalamic-pituitary gonad axis see HPG axis hypothalamic-pituitary-adrenal axis see HPA axis hypothalamic-pituitary-end-organ axes. Germany Mario Maj University of Naples, Italy Norman Sartorius University of Geneva, Switzerland Psychiatry as a Neuroscience Edited by Juan Jose  Lo  pez-Ibor, Wolfgang Gaebel, Mario Maj, . ``He is not mad, his only madness is vice'' [2]. The second step was quite straightforward: to ascribe what was leftÐthat is, mental diseaseÐto an organ, quite naturally the brain. Although